Evidence for Persistent Enterovirus Infection of the Central Nervous System in Patients with Previous Paralytic Poliomyelitis
Evidence for Persistent Enterovirus Infection of the Central Nervous System in Patients with Previous Paralytic Poliomyelitis
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DOI：
10.1111/j.1749-6632.1995.tb27548.x
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发表时间：
1995-05
影响因子：
5.2
通讯作者：
P. Muir;F. Nicholson;M. Sharief;E. Thompson;N. Cairns;P. Lantos;G. Spencer;H. Kaminski;J. Banatvala
中科院分区：
文献类型：
--
作者：
P. Muir;F. Nicholson;M. Sharief;E. Thompson;N. Cairns;P. Lantos;G. Spencer;H. Kaminski;J. Banatvala
有人认为，在某些情况下，脊髓灰质炎后迟发性神经退化可能是由于中枢神经系统的脊髓灰质炎病毒持续感染所致。鉴于此，我们决定确定脊髓灰质炎病毒和其他肠道病毒是否能在中枢神经系统中持续存在。在先前的一项研究中，我们中的一位（M.K.S.）报告了这些患者中一部分中枢神经系统（CNS）持续脊髓灰质炎病毒感染的血清学证据。我们现在使用聚合酶链反应（PCR）研究了这些患者的脑脊液（CSF）中肠病毒RNA序列的存在。在24例临床诊断为脊髓灰质炎后综合征的患者中有3例检测到肠病毒RNA，但在36例稳定型脊髓灰质炎患者中没有检测到肠道病毒RNA，在36例其他非感染性神经系统疾病患者中也没有检测到肠道病毒RNA。所有检测到病毒RNA的3例患者鞘内脊髓灰质炎病毒特异性寡克隆IgM条带水平均较高。在第二项研究中，我们检查了7例麻痹性脊髓灰质炎患者死后经福尔马林固定的中枢神经系统组织。在3例患者的脊髓组织中检测到肠病毒RNA，但在大脑皮层中未检测到。我们现在正在对有晚期恶化证据的患者进行更大规模的前瞻性盲法研究。对前30名患者的分析显示，4名患有不明原因的脊髓灰质炎后迟发性虚弱的患者中有1名在CSF中存在肠病毒RNA， 6名患者中有1名有临床恶化的证据，但20名患者中没有一例没有不明原因的脊髓灰质炎后虚弱迹象。在本研究中，3例因其他原因死亡的患者中，2例的脊髓中也检测到肠病毒RNA。这些研究提供了病毒学证据，证明肠病毒可能在人类中枢神经系统中持续存在。为了充分了解这些发现的生物学和临床意义，需要进一步的研究。
It has been suggested that late onset neurological deterioration after poliomyelitis may be due in some cases to persistent poliovirus infection of the central nervous system. In view of this, we decide to determine whether polioviruses and other enteroviruses can persist in the central nervous system. In a previous study, one of us (M.K.S.) reported serological evidence of persistent poliovirus infection of the central nervous system (CNS) in a proportion of these patients. We have now studied cerebrospinal fluid (CSF) from these patients for the presence of enterovirus RNA sequences using the polymerase chain reaction (PCR). Enteroviral RNA was detected in 3 of 24 patients with a clinical diagnosis of post-polio syndrome, but in none of 36 patients with stable poliomyelitis, and none of 36 patients with other neurological conditions of noninfective origin. All 3 patients in whom viral RNA was detected had high intrathecal levels of poliovirus-specific oligoclonal IgM bands. In a second study we examined formalin-fixed postmortem CNS tissue from 7 patients with a history of paralytic poliomyelitis. Enterovirus RNA was detected in tissue from the spinal cord from 3 patients, but not in the cerebral cortex. We are now conducting a larger prospective, blind study of patients with evidence of late deterioration. Analysis of the first 30 patients studied revealed the presence of enterovirus RNA in CSF of 1 of 4 patients with unexplained late-onset post-polio weakness, 1 of 6 with some evidence of clinical deterioration, but none of 20 without inexplicable signs of post-polio weakness. Enteroviral RNA was also detected in spinal cord from 2 of 3 patients who died from other causes during this study. These studies provide virological evidence that enteroviruses may persist in the CNS of man. Further study is required in order to understand fully the biological and clinical significance of these findings.